Neurometabolic profile of mild cognitive impairment using multiplexed edited MRS

总结 轻度认知障碍（MCI）是阿尔茨海默病（AD）的临床前形式，其特征在于认知功能障碍。 这些缺陷介于健康老龄化和AD中观察到的缺陷之间。遗忘型多域MCI （aMCI-MD）是MCI的一种亚型，具有高（~40%）转化为AD的比率，代表了用于治疗AD的有价值的队列。 在相对早期阶段进行AD病理生理学的机制研究。原发性病理/影像学 在AD/MCI中的发现是脑组织中的异常蛋白沉积，但其机制尚不清楚。 沉积开始并最终导致认知能力下降，人们对此知之甚少。最近的事态发展 在编辑磁共振波谱（MRS）中， 浓度代谢物的关键利益MCI，包括氧化还原化合物（谷胱甘肽和抗坏血酸）， 神经递质和神经调质（GABA、谷氨酸、天冬氨酸和N-乙酰基谷氨酸），以及 其它化合物包括厌氧产物乳酸盐。 在本研究中，我们将应用新的编辑实验HERCULES（Hadamard Editing Resolves Chemicals 使用光谱的线性估计）来测量三种病理重要的组织中这些代谢物的水平。 大脑区域（内侧颞叶，前扣带和后扣带）与aMCI-MD和年龄-和 性别匹配的健康对照。我们还将测试神经化学和 认知结果，以及MRS代谢物水平与淀粉样蛋白-β和tau蛋白的既往PET成像之间的关系 证词

Summary Mild Cognitive Impairment (MCI) is a preclinical form of Alzheimer's Disease (AD), characterized by cognitive deficits that are intermediate between those observed in healthy aging and AD. Amnestic multi-domain MCI (aMCI-MD) is a subtype of MCI with high (~40%) rates of conversion to AD, representing a valuable cohort for mechanistic studies of AD pathophysiology at a relatively early phase. The primary pathological/imaging finding in AD/MCI is of abnormal protein deposition in brain tissue, but the mechanisms by which this deposition is initiated and ultimately results in cognitive decline, are poorly understood. Recent developments in edited magnetic resonance spectroscopy (MRS) have substantially accelerated measurements of low- concentration metabolites of key interest in MCI, including redox compounds (glutathione and ascorbate), neurotransmitters and neuromodulators (GABA, glutamate, aspartate and N-acetylaspartylglutamate), and other compounds including the anaerobic product lactate. In this study, we will apply the new editing experiment HERCULES (Hadamard Editing Resolves Chemicals Using Linear Estimation of Spectra) to measure levels of these metabolites in three pathologically important brain regions (medial temporal lobe, anterior and posterior cingulate) in subjects with aMCI-MD and age- and sex-matched healthy controls. We will also test hypothesized relationships between neurochemistry and cognitive outcomes, and between MRS metabolite levels and prior PET imaging of amyloid-β and tau protein deposition.